L-methylfolate is crucial to DNA synthesis and detoxifying homocysteine. It can also improve a variety of mental disorders including depression and schizophrenia.

Read on to see if you should be supplementing with L-methlyfolate.

What is L-Methylfolate

Folate, otherwise known as vitamin B9, is one of the 13 essential vitamins. Vitamins come in different forms called vitamers that often need to be converted in the body to active forms of the vitamin. The active form of folate in the body is L-methylfolate, also known as levomefolic acid, which can cross both cell membranes and the blood-brain barrier [R].

A critical role of L-methylfolate is to act as a regulator of a class of neurotransmitters called monoamines. The three different neurotransmitters it helps make are [R]:

  • Serotonin
  • Dopamine
  • Norepinephrine

Folate can’t be synthesized by the body, so it must be ingested either through food or supplements [R].

The synthetic form of folate is folic acid, which can be found in fortified foods such as bread and cereals, and multivitamins [R, R].

Dihydrofolate is the dietary form of folate and can be found in green vegetables, egg yolk, legumes, grains, nuts, some fruits, yeast, and organ meats like liver and kidneys [R, R].

Both folic acid and dihydrofolate are converted into L-methylfolate in the body by a specific enzyme. It is then transported into the brain where it increases the production of the three neurotransmitters mentioned above [R].

Folic acid supplementation and unmetabolized folic acid have been associated with increased incidence of prostate cancer, lower cognitive test scores, and smaller red blood cells [R, R].

Methylfolate is responsible for many methylation reactions all throughout the body. Methylation reactions occur when methylfolate donates a methyl group (three hydrogens bonded to one carbon atom) to another molecule [R].

Methylation reactions are crucial for processes such as cell division and DNA and RNA synthesis. Methylation of DNA and RNA plays a crucial role in epigenetics, which is a change in gene activity without changes to the underlying genetics [R].

Although many people take L-methylfolate supplements, much of the naturally ingested L-methylfolate actually comes in the form of different folates such as folic acid and dihydrofolate [R,R].

The conversion of these folates to L-methylfolate is crucial because L-methylfolate can cross the blood-brain barrier, while the other forms of folate can’t [R].

L-methylfolate is commonly used to slow cognitive decline that is seen in many mental disorders, including Alzheimer’s, mania, and depression. Many of these disorders are linked to mutations in the gene that produce the enzyme that converts folate into L-methylfolate,  5, 10-methylenetetrahydrofolate (MTHFR) [R, R, R, R].

Mutations in MTHFR can lead to decreased methylfolate production. Mutations in MTHFR are very common and there are up to 30 different kinds of MTHFR mutation variations [R].

Mechanisms of Action

L-Methylfolate is responsible for:

  • Methylation [R]
  • DNA/RNA synthesis [R]
  • Conversion of homocysteine to methionine [R]
  • Homocysteine is a toxic amino acid that is particularly damaging to blood vessels (endothelial cells). High levels of homocysteine lead to increased inflammation and risk of coronary heart disease [R]
  • L-methylfolate methylates homocysteine into the less-toxic methionine, an essential amino acid [R]

L-Methylfolate Health Benefits

1) L-methylfolate Can Help Treat Depression

In a study (DB-RCT) of 123 patients with either depression or schizophrenia, a large portion of them had folate deficiencies [R].

Patients with folate deficiencies were given either methylfolate or placebo. The patients given methylfolate improved significantly compared to placebo both clinically and socially, especially in mood, and the difference in improvements increased with time [R].

In a study (DB-RCT) of 68 depression patients who did not respond to antidepressants (selective serotonin reuptake inhibitors, or SSRI), 15 mg/day of L-methylfolate was given for 12 months. Of the 68 patients, 26 had a full recovery from their depression and 35 experienced a reduction in the severity of their depression (remission) [R].

None of the patients who had a full recovery experienced a relapse or recurrence of their symptoms during the trial [R].

In one study, 147 patients given only SSRIs were three times more likely to become hospitalized than patients given SSRIs plus L-methylfolate supplements [R].

Depression can be caused by a number of different factors. This explains why certain drugs and supplements work for some people and not others. L-methylfolate supplementation is more effective in depression patients with these traits [R]:

  • Decreased levels of folate or any other folate by-products in the blood
  • Unresponsive to common antidepressants
  • Low folate levels as a result of:
    • Alcohol addiction
    • Eating disorders
    • Pregnancy
    • Gut disorders
    • High homocysteine levels
    • Drugs that interfere with folate metabolism

When homocysteine is converted to methionine by L-methylfolate, S-adenosylmethionine (SAM-e) concentrations rise. SAM-e is responsible for donating methyl groups to fat molecules that line our cell membranes and in the formation of the neurotransmitter serotonin [R].

L-Methylfolate Can Help Those with Bipolar 1 Depression

The Montgomery Asberg Depression Rating Scale (MADRS) is used to measure the degree of depression in patients with a higher score number being worse [R].

In a study of 10 patients with bipolar depression, L-methylfolate in combination with conventional treatment reduced the average MADRS score from 23.4 to 13.9 [R].

Six out of the 10 patients showed at least a 50% improvement in MADRS score and the other four experienced a reduction in the severity of their depression (remission) [R].

2) L-methylfolate Can Help With Schizophrenia

In a study of 91 schizophrenic patients, there was a link between the severity of the negative symptoms of schizophrenia and low blood levels of folate [R].

It was hypothesized that the link was due to poor diet and more cigarette smoking in schizophrenic patients [R].

Indeed, cigarette smoking was linked to decreased levels of folate [R].

In a study (DB-RCT) of 140 schizophrenic patients, only those given folic acid with vitamin B12 supplementation (and a specific mutation of the FOLH1 gene) improved negative symptoms considerably. The FOLH1 gene is one of the genes responsible for metabolizing methylfolate [R].

All the patients in the previously mentioned study had been on antischizophrenic drugs for six months prior or longer but had shown no improvements in symptoms [R].

In another study (DB-RCT) of 35 schizophrenic patients, L-methylfolate not only improved symptoms but also produced beneficial changes in the brain [R].

The patients given L-methylfolate supplements showed increased cortical thickness in the medial prefrontal cortex (mPFC), which was correlated to a partial restoration of structure and function of the mPFC [R].

The medial orbitofrontal cortex (mOFC), which normally deactivates during tasks requiring working memory, is dysfunctional in schizophrenic patients. The patients receiving L-methylfolate supplementation showed increased deactivation [R].

Schizophrenia can be due to many different factors. This is the reason why one of the studies only found positive effects in those with FOLH1 gene mutations [R].

3) L-Methylfolate Can Help With Alzheimer’s Disease

People with Alzheimer’s disease are more likely to have reduced folate levels compared to healthy people. Therefore, L-methylfolate supplements can improve symptoms in those patients [R].

Alzheimer’s disease is also brought about by increased inflammation in the brain due to higher levels of tumor necrosis factor (TNF)-α, an inflammatory molecule, and amyloid beta plaques. In a study (SB-RCT) of 121 patients, L-methylfolate greatly reduced levels of TNF-α and amyloid beta [R].

In a recent clinical trial of 30 Alzheimer’s and dementia patients, L-methylfolate greatly reduced brain deterioration in the hippocampus and cortical areas of the brain [R].

The conversion of homocysteine slowed brain deterioration and improved cognitive functions such as learning and memory [R].

The study indicated that treatment for at least one year is usually necessary to slow decline [R].

4) L-Methylfolate Can Reduce Mania

Mania is a state of heightened arousal, elevated mood, and increased energy.

The Young Mania Rating Scale (YMRS) is used to score mania with higher numbers signifying worse mania [R].

In a study of 10 manic and bipolar depressed patients, L-methylfolate reduced the average pre-treatment YMRS from 3.2 to 2.7 [R].

5) L-Methylfolate Improves Pregnancy Outcomes

L-methylfolate is crucial for pregnant women as it helps reduce the risk of developing different disorders that can occur in both the fetus and the mom. Because of the importance of supplementation, the U.S. government began mandating the addition of more folic acid into grain products (140µg/100g) in January 1998 [R, R].

L-Methylfolate Supplementation can Help Prevent Neural Tube Defect (NTD)

L-Methylfolate supplementation helps prevent neural tube defect, which are defects of the brain, spine, and spinal cord [R].

It is advised for women that are more at risk for NTD to take 5mg daily and all other pregnant women to take 0.4-1mg daily [R].

L-Methylfolate Supplementation can Help Prevent Anemia

Pregnant women usually have reduced hemoglobin (protein that carries oxygen in the blood) levels, which leads to anemia in 5% of pregnancies [R].

In a study of 58 pregnant women taking prenatal supplements along with L-methylfolate had significantly higher hemoglobin levels at the time of delivery than 54 women only taking prenatal supplements [R].

L-Methylfolate May Prevent Preterm Birth

Low blood folate levels have been linked to shorter pregnancy times [R].

A study of 34,480 women found that supplementing with L-methylfolate for longer than one year significantly decreased the chances of preterm birth. The length of L-methylfolate supplementation (> 1 year) was equally as important as supplementing itself [R].

Other

Supplementing with L-methylfolate has also been shown to reduce risks of other pregnancy problems such as heart defects and orofacial clefts, which are openings that may form in the mouth and lip [R, R].

6) L-Methylfolate Can Boost the Immune System

T cells are key cells involved in the innate immune system, the part of the immune system that provides short-term defense against pathogens. A cell study showed that folate deficiency led to decreased production of T-cells [R].

Increasing folate levels increased the T-cell levels to normal levels [R].

Other studies have shown that deficiencies in folate also lead to decreased responses of T-cells and antibodies to certain pathogens. This ultimately leads to decreased resistance to infections [R].

7) L-Methylfolate May Improve Autism

Mutations in the gene encoding the enzyme 5,10-methylenetetrahydrofolate (MTHFR) disrupt the enzyme’s ability to convert folic acid into L-methylfolate. L-methylfolate decreased symptoms of aggressive and disruptive behavior in an autistic child with a MTHFR C667T mutation [R].

Further studies need to be done to validate these results.

Side Effects and Risks of L-Methylfolate

Common side effects of L-methylfolate include [R]:

  • dry mouth
  • fatigue
  • headache

Overconsumption of L-methylfolate can mask vitamin B12 deficiencies [R].

L-Methylfolate Dosage

Many of the commercial L-methylfolate supplements contain between 5,000 mcg (5 mg) and 1,000 mcg (1 mg) [R,R].

However, many studies have used doses of up to 15 mg to see intended effects [R].

Please consult your physician to determine the correct dosage to address your health issues.

Drug Interactions

1) Drugs That May Interfere with L-Methylfolate Absorption

Certain drugs can decrease folate levels leading to decreased L-methylfolate concentrations in the brain due to interfering with absorption. Some examples are listed below [R]:

  • Antacids
  • Alcohol
  • Oral contraceptives
  • Metformin
  • Some statin drugs
  • Anticonvulsants
    • Valproate
    • Carbamazepine
    • Phenytoin
    • Lamotrigine

A study done on 36 children taking Carbamazepine and 30 children taking Valproate showed that these medications reduced folic acid levels in the blood significantly [R].

The loss of folic acid led to significantly higher levels of homocysteine in the children taking Valproate and Carbamazepine [R].

2) L-Methylfolate Supplementation May Reduce the Effectiveness of Methotrexate

Methotrexate has been used to treat psoriasis, which is a disease that causes the formation of red patches on the skin with silver plaques and scales, for over 40 years [R].

However, methotrexate works by inhibiting dihydrofolate reductase (DHFR), an enzyme that metabolizes folic acid. Therefore, L-methylfolate supplementation can work to counteract the mechanisms by which methotrexate heals [R].

A case study on one patient taking both methotrexate for his psoriasis and L-methylfolate for his depression showed the patient developed psoriatic lesions after taking L-methylfolate. Only when the patient stopped taking methotrexate did the lesions disappear [R].

L-Methylfolate in Combination With Other Drugs and Supplements

1) L-Methylfolate Supplementation Enhances Effects of Antidepressants

A study comparing L-methylfolate plus selective serotonin reuptake inhibitors (SSRI, a common antidepressant) therapy (95 patients) with just SSRI therapy (147 patients) showed that adding L-methylfolate greatly enhanced results [R].

For instance, discontinuation rates for L-methylfolate plus SSRI were 17.9% compared to 34% for only SSRI therapy [R].

By 60 days, major improvement was seen in up to 18.5% of patients on L-methylfolate plus SSRI patients while only 7% of patients on just SSRI showed improvements [R].

The time it took until major improvements showed was 177 days for the patients on L-methylfolate plus SSRI compared to 231 days for patients solely on SSRI [R].

The combined therapy also showed that patients were more likely to adhere to the therapy and there were fewer people that refused treatment due to lower rates of adverse events [R].

2) L-Methylfolate Supplementation with Vitamin B12 and N-acetylcysteine Delays Brain Deterioration in Alzheimer’s Disease

A study on 67 patients with Alzheimer’s disease showed that L-methylfolate supplementation with vitamin B12 and N-acetylcysteine significantly slowed deterioration in the brain [R].

3) L-Methylfolate Supplementation Improves the Beneficial Effects of Cholinesterase Inhibitors (ChI) in Alzheimer’s Patients

Cholinesterase inhibitors prevent the enzyme cholinesterase from breaking down the neurotransmitter acetylcholine.

In a study (DB-RCT) of 57 Alzheimer’s patients, folic acid supplementation was studied to see if it could boost the effects of ChI therapy [R].

The patients given both folic acid and ChI therapy significantly improved in performing daily living activities and in social behavior compared to patients only given ChI therapy [R].

4) L-Methylfolate Supplementation with Donepezil may Boost Effects on Those with Vascular Dementia

Folate supplementation along with Donepezil (used to treat Alzheimer’s disease) and natrium diethyldithiocarbamate trihydrate (NDDCT) greatly improved symptoms in those with vascular dementia [R].

The increased effects were seen in the areas of learning, memory, and endothelial dysfunction [R].

Contraindications of L-Methylfolate Supplements

The L-methylfolate can invoke an allergic response to those that are allergic to folic acid. This was experienced by one user in a review board [R].

Otherwise, there are no specific contraindications to L-methylfolate supplementation.

SNPs That Can Reduce L-Methylfolate Levels

The enzyme 5,10-methylenetetrahydrofolate (MTHFR) is responsible for the conversion of folate or folic acid into L-methylfolate. Mutations in the gene responsible for MTHFR creation lead to decreased L-methylfolate production [R].

Humans have two copies of each gene and different forms of the same gene are called alleles.

There are up to 30 different kinds of mutations in the MTHFR gene. Up to 60% of Americans carry at least one allele with a mutation in the MTHFR gene (heterozygous).

One common mutation is called C677T and it is prevalent in up to 10% of the white people and up to 22% of the Hispanics and Mediterranean populations. Having one allele with this mutation decreases MTHFR activity by up to 35%, while having two alleles with this mutation (homozygous) decreases activity by 70% [RR].

One male patient suffering from depression, mania, and obsessive-compulsive disorder (OCD) was screened and found with a MTHFR C677T mutation. Common medications were tried and failed to produce results. Only after L-methylfolate supplementation did the male patient showcase improvements [R].

Another common mutation called A1298C also reduces MTHFR activity [R]. Individuals with two alleles with this mutation show 68% reduced activity in the MTHFR enzyme [R].

Patients suffering from schizophrenia and bipolar disorder are even more likely than depressed patients to have MTHFR mutations [R].

Supplementing with L-methylfolate bypasses all MTHFR mutations and increases methylation reactions throughout the body [R].

Mutations in the FOLH1 gene can also result in reduced folate levels due to impaired absorption of folate in the gut [R].

L-Methylfolate User Reviews

A review of those taking L-methylfolate supplements found that it was most helpful for those that were taking the supplement for depression, folic acid deficiencies, and borderline personality disorder.

Some users liked the L-methylfolate because it produced fewer symptoms than other antidepressants such as Lexapro while others still complained about some symptoms such as dry coughs, blurred vision, and dizziness.

One user said that after getting a genetic test and finding out that he/she had a genetic mutation that lowered folate levels, taking L-methylfolate has been one of the most successful antidepressant treatments yet. The user had already tried up to 30 different antidepressants and liked this one the best.

Possibly undergoing genetic tests to see if your depression is caused by folate deficiencies could be a good place to start to see whether or not L-methylfolate supplements are right for you.

Other sites have had mixed reviews as well with many people either very for the supplement or completely against it.

FDA Compliance

The information on this website has not been evaluated by the Food & Drug Administration or any other medical body. We do not aim to diagnose, treat, cure or prevent any illness or disease. Information is shared for educational purposes only. You must consult your doctor before acting on any content on this website, especially if you are pregnant, nursing, taking medication, or have a medical condition.

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10 COMMENTS

  • Nattha Wannissorn, PhD

    You mean folic acid? Safest bet is whole foods form of folate, like chicken liver.

  • Ted Hu

    I’ll add to the details comments earlier.

    There are other nuances this post misses.

    I propose downloading and reviewing Yasko diagrams on the topic.

    For one, it’s not accurate to say methyl folate is responsible for methylation.

    The methhylfolate cycle works with MB12 to help recycle spent methyl donors used in the primary methyl cycle. Think of two spinning particle fields thousands of times a second interacting at intracellular level.

    MB12 help recycle MF which in turn replenish spent methyl donors eg homecysteine that was once choline/DMG/TMG/SAM-e->methionine which donate their methyl molecules for methylation as well as to the transsulfuration cycle which drives taurine to glutathione production, after which a spent methyl donee that is homecysteine becomes a reactant that needs to be replenished.

    There are many papers that talk about the import of various cholines (CDP, AGPC, etc.) and methyl donors (TMG, DMG, SAM-E) and how they help spare Methylfolate and vice versa, but they are *not* co-equivalent substitutes.

    Methylfolate if anything is more key to driving the BH4BH2 cycle that is precursors to the three horsemen neurotransmitters cited above which is related to methylation insofar as methylated serotonin transforms into melatonin for example.

    I would review methylation diagrams and include that in these posts. I think visually, and translate math and physics into cause and effect process diagrams, while also mastering the equations. Depending on how one is wired, the right diagram(s) will help make these complex concepts more precise as words are too easily overloaded.

    I continue to rely on Yasko diagrams and consider them central to any supplementation regime. Genetic mutations are static decision points. Biology is a dynamic flow and should be discussed thusly.

  • Will Hunter

    Thank you, Usood, for pointing this out. I have changed the article to accurately reflect the source.

  • Will Hunter

    Thank you, Carol, for pointing out those inaccuracies. I have corrected the article accordingly.

  • carol close

    The take away. Good> methylfolate- bad> folic acid. This article needs to make the conclusions clearer. You have underestimated and need to point out the numbers of people who have at least one copy of the MTHFR gene defect (85%) discovered in the recent Human Genome Project.  So, pretty much the whole world needs methylfolate. And- Do not take folic acid!

    You are missing the point.  People should throw out their multi-vitamins because the cheap synthetic folic acid in the vitamins build up in the body, so it can cause major health problems- birth defects, cancer, cardiovascular disease, and dementia because most people have a reduced ability or can not methylate cheap synthetic folic acid or folate into methylfolate because they have a MTHFR gene defect copy.

    Keep in mind that a deficiency of the good stuff- methylfolate, causes side effects- including stomach problems and inflammation, hair loss, anemia, and high homocysteine levels which are linked to heart disease, vascular dementia, erectile dysfunction, depression, and cancer. Doctors can give you a prescription of Metanx or buy Life Extension 2 Per Day Vitamins or similar vitamins that have methylfolate, plus buy betaine, or buy methylfolate also known as 5-MTHF plus betaine also known as TMG.  The reason- You also need betaine or TMG with the methylfolate to reduce homocysteine levels as methylfolate alone does not reduce homocysteine. Do not eat vitamin supplements with folic acid- the bad stuff. It causes cancer! Throw out your vitamins. Do not eat foods fortified with extra folic acid found in bread, cereal, flour, cornmeal, pasta, rice, and other grain.  It is so bad that as little as 5 mg a day of folic acid for 90 days increases serum unmetabolized folic acid which causes reduced natural killer cell cytotoxicity which causes cancer and reduces defenses against virus infections in humans.  

    MTHFR mutation which up to 85% of us may have, increases the risk of cardiovascular disease and vitamin B deficiencies due to high homocysteine levels. Those with an MTHFR mutation are at risk for poor MTHFR enzyme efficiency. Consequently, folate and folic acid cannot be efficiently converted into their active form, known as 5-MTHF or L-methylfolate. So, those who have a MTHFR gene defect  (which most of us in the whole world have) can not process folate and especially folates in the form of cheap synthetic folic acid found in normal vitamins into methylfolate. Do not underestimate how important proper methylation is and how sick and closer to death we get if we are deficient our whole life long. Methylation is needed to stop high levels of homocysteine for cardiovascular health, vascular dementia, and erectile dysfunction. Methylation is needed to decrease inflammation for every disease we do not want to get. Methylation is needed for DNA stabilization in DNA replication, so we are reproducing healthy cells needed to regenerate our bodies. Methylation is needed to keep telomeres long and to keep us from aging rapidly. Methylation is needed to make neurotransmitters like serotonin, dopamine and norepinephrine to stop neurodegeneration, dementia and prevent psychiatric illnesses. Methylation is needed to make hormones in our mitochondria which mitochondria are the power house of every cell.http://www.gbhealthwatch.com/GND-Cardiovascular-Diseases-MTHFR.php
    Two common variants of the MTHFR gene, 677C>T and 1298 A>C, lead to reduced enzyme activity and increased risk for hyperhomocysteinemia, cardiovascular diseases and cancer. The distributions of these two variants are quite high, with frequencies between 13 to 57% depending on ethnic group (Table 1). Overall, about 85% OF THE GENERAL POPULATION CARRIES AT LEAST ONE OF THESE MTHFR VARIANTS.  In addition, functional interaction between these two variants results in an additive effect on MTHFR enzyme activity. The compound heterozygous genotype, which refers to people carrying both variants is found in between 14% and 23% of people within most ethnic groups (Table 1) and can reduce enzyme activity by up to 48%. (Note: your articles only uses the 14% and 23% figures and saying it wrong with the MTHR C667 gene mutation, so your conclusion has no impact.)
    https://www.ncbi.nlm.nih.gov/pubmed/27012626 “High folic acid reduces natural killer cell cytotoxicity in aged mice.” note: Low natural killer cell number or function in elderly individuals is associated with increased mortality risk and increased incidence of severe infections, supporting the role of natural killer cells in the defense against infections in the elderly.
    https://www.ncbi.nlm.nih.gov/pubmed/23482308 “Is 5-methyltetrahydrofolate an alternative to folic acid for the prevention of neural tube defects?” Yes. Methylfolate is better than folic acid.
    https://www.ncbi.nlm.nih.gov/pubmed/28895788 “Association between Serum Unmetabolized Folic Acid Concentrations and Folic Acid from Fortified Foods.”
    https://www.ncbi.nlm.nih.gov/pubmed/20727555 “Concentrations of unmetabolized folic acid and primary folate forms in plasma after folic acid treatment in older adults.”
    https://www.ncbi.nlm.nih.gov/pubmed/25733468 “Unmetabolized folic acid is detected in nearly all serum samples from US children, adolescents, and adults.”
    https://www.ncbi.nlm.nih.gov/pubmed/28724658 “A Daily Dose of 5 mg Folic Acid for 90 Days Is Associated with Increased Serum Unmetabolized Folic Acid and Reduced Natural Killer Cell Cytotoxicity in Healthy Brazilian Adults.”
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3610948/ “Betaine supplementation decreases plasma homocysteine in healthy adult participants: a meta-analysis.”

  • carol close

    Here is something to add. Alcohol and these drugs may stop methylation because they inhibit folic acid absorption in the stomach, reduce absorption of B vitamins, inactivate B vitamins, may make you deficient in B vitamins, elevate homocysteine, cause folate deficiency, can inhibit expression of the reduced folate carrier and decrease the hepatic uptake and renal conservation of circulating folate,  etc.  In other words, alcohol and these listed drugs below can stop methylation which is important for DNA replication and mitochondrial function. They can affect hormone synthesis in mitochondria, affect your body’s ability to make neurotransmitters, increase inflammation in our bodies, cause high homocysteine, heart disease, erectile dysfunction, dementia, neurodegeneration and psychiatric disorders. Alcohol and drugs that detrimentally affect methylation for those with the MTHFR defect: Antacids, proton pump inhibitors, histamine blockers, anti-depressants/SSRIs, statins, cholesterol lowering medications, amalgram fillings, fluoride, acetaminophen, fish oil, asthma medications-Theophylline, albuterol and prednisone, Anticonvulsants, Cyclosporine, Methotrexate, Dilantin, Neuroleptics Colchine, Oral diabetic medications-Metformin, Ethionamid, Cycloserine, Aminosalicylic acid, Antibiotics, phenytoin, fosphenytonin, phenobarbital, cobalt, chlorpromazine, methylprednizone, synthetic hormone birth control, levodopa, antihypertensives, methotrexate. Asthma medications-Theophylline, albuterol, prednisone.

    This article should stress the importance of methylation. This article should actually be a wake up call to the supplement industry to reformulate vitamins to take out folic acid which kills natural killer cells that reduce defenses against viruses and causes cancer, and replace folic acid with methylfolate; otherwise Life Extension vitamins will take away all of their business and doctors will be prescribing Metanx instead.  This article should be a wake up call to the pharmaceutical industry that their drugs inhibit methylation and change our epigenetics in deleterious and permanent ways with tragic and enduring side effects.  Drugs should be taken off the market by the FDA if they cause more diseases than they cure.

    http://www.medicinabiomolecular.com.br/biblioteca/pdfs/Nutrigenomica/nutrig-0043.pdf “Epigenetic side effects of common pharmaceuticals: a potential new field in medicine and pharmacology.” Epigenetics refers to DNA and chromatin Here is something to add. Alcohol and these drugs may stop methylation because they inhibit folic acid absorption in the stomach, reduce absorption of B vitamins, inactivate B vitamins, may make you deficient in B vitamins, elevate homocysteine, cause folate deficiency, can inhibit expression of the reduced folate carrier and decrease the hepatic uptake and renal conservation of circulating folate,  etc.  In other words, alcohol and these listed drugs below can stop methylation which is important for DNA replication and mitochondrial function. They can affect hormone synthesis in mitochondria, affect your body’s ability to make neurotransmitters, increase inflammation in our bodies, cause high homocysteine, heart disease, erectile dysfunction, dementia, neurodegeneration and psychiatric disorders. Alcohol and drugs that detrimentally affect methylation for those with the MTHFR defect: Antacids, proton pump inhibitors, histamine blockers, anti-depressants/SSRIs, statins, cholesterol lowering medications, amalgram fillings, fluoride, acetaminophen, fish oil, asthma medications-Theophylline, albuterol and prednisone, Anticonvulsants, Cyclosporine, Methotrexate, Dilantin, Neuroleptics Colchine, Oral diabetic medications-Metformin, Ethionamid, Cycloserine, Aminosalicylic acid, Antibiotics, phenytoin, fosphenytonin, phenobarbital, cobalt, chlorpromazine, methylprednizone, synthetic hormone birth control, levodopa, antihypertensives, methotrexate. Asthma medications-Theophylline, albuterol, prednisone.

    This article should stress the importance of methylation. This article should actually be a wake up call to the supplement industry to reformulate vitamins to take out folic acid which kills natural killer cells that reduce defenses against viruses and causes cancer, and replace folic acid with methylfolate; otherwise Life Extension vitamins will take away all of their business and doctors will be prescribing Metanx instead.  This article should be a wake up call to the pharmaceutical industry that their drugs inhibit methylation and change our epigenetics in deleterious and permanent ways with tragic and enduring side effects.  Drugs should be taken off the market by the FDA if they cause more diseases than they cure.

    http://www.medicinabiomolecular.com.br/biblioteca/pdfs/Nutrigenomica/nutrig-0043.pdf “Epigenetic side effects of common pharmaceuticals: a potential new field in medicine and pharmacology.” Epigenetics refers to DNA and chromatin Here is something to add. Alcohol and these drugs may stop methylation because they inhibit folic acid absorption in the stomach, reduce absorption of B vitamins, inactivate B vitamins, may make you deficient in B vitamins, elevate homocysteine, cause folate deficiency, can inhibit expression of the reduced folate carrier and decrease the hepatic uptake and renal conservation of circulating folate,  etc.  In other words, alcohol and these listed drugs below can stop methylation which is important for DNA replication and mitochondrial function. They can affect hormone synthesis in mitochondria, affect your body’s ability to make neurotransmitters, increase inflammation in our bodies, cause high homocysteine, heart disease, erectile dysfunction, dementia, neurodegeneration and psychiatric disorders. Alcohol and drugs that detrimentally affect methylation for those with the MTHFR defect: Antacids, proton pump inhibitors, histamine blockers, anti-depressants/SSRIs, statins, cholesterol lowering medications, amalgram fillings, fluoride, acetaminophen, fish oil, asthma medications-Theophylline, albuterol and prednisone, Anticonvulsants, Cyclosporine, Methotrexate, Dilantin, Neuroleptics Colchine, Oral diabetic medications-Metformin, Ethionamid, Cycloserine, Aminosalicylic acid, Antibiotics, phenytoin, fosphenytonin, phenobarbital, cobalt, chlorpromazine, methylprednizone, synthetic hormone birth control, levodopa, antihypertensives, methotrexate. Asthma medications-Theophylline, albuterol, prednisone.

    This article should stress the importance of methylation. This article should actually be a wake up call to the supplement industry to reformulate vitamins to take out folic acid which kills natural killer cells that reduce defenses against viruses and causes cancer, and replace folic acid with methylfolate; otherwise Life Extension vitamins will take away all of their business and doctors will be prescribing Metanx instead.  This article should be a wake up call to the pharmaceutical industry that their drugs inhibit methylation and change our epigenetics in deleterious and permanent ways with tragic and enduring side effects.  Drugs should be taken off the market by the FDA if they cause more diseases than they cure.

    http://www.medicinabiomolecular.com.br/biblioteca/pdfs/Nutrigenomica/nutrig-0043.pdf “Epigenetic side effects of common pharmaceuticals: a potential new field in medicine and pharmacology.” Epigenetics refers to DNA and chromatin modifications that persist from one cell division to the next, despite a lack of change in the underlying DNA sequence. The “epigenome” refers to the overall epigenetic state of a cell, and serves as an interface between the environment and the genome. The epigenome is dynamic and responsive to environmental signals not only during development, but also throughout life; and it is becoming increasingly apparent that chemicals can cause changes in gene expression that persist long after exposure has ceased. Here we present the hypothesis that commonly-used pharmaceutical drugs can cause such persistent epigenetic changes. Drugs may alter epigenetic homeostasis by direct or indirect mechanisms. Direct effects may be caused by drugs which affect chromatin architecture or DNA methylation. For example the antihypertensive hydralazine inhibits DNA methylation. An example of an indirectly acting drug is isotretinoin, which has transcription factor activity. A two-tier mechanism is postulated for indirect effects in which acute exposure to a drug influences signaling pathways that may lead to an alteration of transcription factor activity at gene promoters. This stimulation results in the altered expression of receptors, signaling molecules, and other proteins necessary to alter genetic regulatory circuits. With more chronic exposure, cells adapt by an unknown hypothetical process that results in more permanent modifications to DNA methylation and chromatin structure, leading to enduring alteration of a given epigenetic network. Therefore, any epigenetic side-effect caused by a drug may persist after the drug is discontinued. It is further proposed that some iatrogenic diseases such as tardive dyskinesia and drug-induced SLE are epigenetic in nature. If this hypothesis is correct the consequences for modern medicine are profound, since it would imply that our current understanding of pharmacology is an oversimplification. We propose that epigenetic side-effects of pharmaceuticals may be involved in the etiology of heart disease, cancer, neurological and cognitive disorders, obesity, diabetes, infertility, and sexual dysfunction. It is suggested that a systems biology approach employing microarray analyses of gene expression and methylation patterns can lead to a better understanding of long-term side-effects of drugs, and that in the future, epigenetic assays should be incorporated into the safety assessment of all pharmaceutical drugs. This new approach to pharmacology has been termed “phamacoepigenomics”, the impact of which may be equal to or greater than that of pharmacogenetics. We provide here an overview of this potentially major new field in pharmacology and medicine.

    http://suzycohen.com/articles/methylation/ “Medicine Messes Up Your Methylation.”

    http://drhyman.com/blog/2011/02/08/maximizing-methylation-the-key-to-healthy-aging-2/

    http://www.drkendalstewart.com/wp-content/uploads/2011/09/Methylation-Overview-for-Professionals-10.11.pdf

    http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=download&path%5B%5D=2441&path%5B%5D=4386 “Selected drugs that inhibit DNA methylation can preferentially kill p53 deficient cells.”  (p53 is the tumor suppressor gene.)

    http://www.nature.com/scitable/topicpage/The-Role-of-Methylation-in-Gene-Expression-1070 (Not all genes are active at all times. DNA methylation is one of several epigenetic mechanisms that cells use to control gene expression.)

  • carol close

    This blog should be rewritten for a couple of changes. At the top, you say, “However, consuming too much L-methylfolate is linked to cancer and certain brain disorders. Read on to see if you should be supplementing with L-methlyfolate.”  False assumption in your second paragraph.  The conclusion should be “However, consuming too much folic acid is linked to cancer and certain brain disorders. Read on to see if you should be supplementing with L-methylfolate.”
    Please reread that your source cites folic acid, not methylfolate. Big mistake.

    Also, in your section…Methylfolate is responsible for many methylation reactions all throughout the body. ….The last sentence- You say, “A large part of the United States population has these mutations with 10-15% of Whites and 25% of Hispanics carrying the mutation MTHFR C667T, one of the more common mutations [R].”   It should say MTHFR C677, not 667.  However, your source says these statistics are only actually for one small particular variant with a double allele. I quote instead from your referenced ncbi source of what it actually says, “More than 25% of Hispanics and around 10-15% of North America Caucasians are estimated to be homozygous for the “thermolabile” variant (TT genotype) (4). The TT genotype is least common in individuals of African descent (6%) (5, 6).”    So you are quoting this completely wrong, plus drawing wrong conclusions.

    Corrections.
    Under….  SIDE EFFECTS AND RISKS OF METHYLFOLATE….. It says, “Furthermore, over-consumption of L-methylfolate (>148 pmol/L in the blood) has been linked to cancer, depression, and other cognitive disorders [R].”  Please re- Read that your source actually says folic acid, not methylfolate……Your source actually says, “…unmetabolized synthetic folic acid with regard to cancer, depression, and cognitive impairment. With all these concerns, early data suggest supplementation with l-methylfolate rather than folic acid may mitigate these risks.”

  • usood

    You state that “Furthermore, over-consumption of L-methylfolate (>148 pmol/L in the blood) has been linked to cancer, depression, and other cognitive disorders (R)”.

    However the reference that you gave for that clearly states “Also, concerns have been raised about the potentially untoward effects of unmetabolized synthetic folic acid with regard to cancer, depression, and cognitive impairment.”

    Clearly unmetabolized synthetic folic acid has these issues, not methylfolate. All the more reason not to take the synthetic folic acid,

  • DavidRN

    I have taken Methotrexate for about 15 years for Rheumatoid Arthritis, until 3 years ago I took 3mg of Folic acid daily with it. I discovered I was MTHFR+ (1298AC) and shifted over to MethylFolate and MethylB12. As I understood it, Methotrexate depletes the body of Folic acid and requires replacement, hence my rationale for continuing. Any thoughts on what is best practice now?

  • mentologo@hotmail.com

    Is part of Martin Pall´s protocole for autoinmune illnesses. Also for EHS electrohipersensitives.

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